This invention relates to the use of xcex1-linolenic acid metabolites for the treatment of cancer. More specifically, this invention relates to the use of stearidonic acid for treatment or prevention of cancer, particularly epithelial cell cancers such as, colon cancer, breast cancer, lung cancer and prostate cancer.
There are two types of essential fatty acids (EFAs), the n-3 (or xcfx89-3) type derived from xcex1-linolenic acid and the n-6 (or xcfx89-6) type derived from linoleic acid. The starting polyunsaturated fatty acids (PUFAs) of these metabolic pathways (i.e., xcex1-linolenic acid and linoleic acid) cannot be produced in the body, and therefore must be obtained in the diet. The desaturation and elongation pathways for the n-3, n-6 and n-9 PUFAs are shown below. 
An important factor providing evidence that dietary fats can have a significant effect on tumorigenesis is data which suggest that the type of fat in the diet may be as important as the quantity of fat in mediating tumor promotion. In this regard, a great deal of attention has been focused on PUFAs. Although the precise mechanisms responsible for the effects of PUFAs are unknown, it has been suggested that PUFA effects are mediated through arachidonic acid, possibly via prostaglandins, HETEs and leukotrienes.
It has long been known that dietary n-3 PUFAs are very effective in depressing tissue arachidonic acid content, and that the long chain n-3 PUFAs are more effective than xcex1-linolenic acid. Whelan, J., Broughton, K. S. and Kinsella, J. E., Lipids, Vol. 26, 119-126 (1991); Hwang, D. H., Boudreau, M. and Chanmugan, P., J. Nutra., Vol. 118, 427-437 (1988). In addition, diets containing n-3 PURAs, particularly those found in fish oils (i.e., eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)), are reported to diminish tumor formation and promotion, and n-3 PURA intake is negatively correlated with chemically-induced tumorigenesis. Braden, L. M. and Carroll, K. K., Lipids 21:285-288, 1986; Reddy, B., and Maruyama, H., Cancer Res. 46:3367-3370, 1986; Minoura, T., Takata, T., Sakaguchi, M., Takada, H., Yamamura, M., Hicki, K. and Yamamoto, J., Cancer Res. 48:4790-4794, 1988; Nelson, R. L., Tanure, J. C., Andrianopoulos, G., Sourza, S. and Lands, W. E. M., Nutr. Cancer 11:215-220, 1988; Reddy, B. and Sugle, S., Cancer Res., 48:6642-6647, 1988.
Tissue arachidonic acid content is correlated with eicosanoid biosynthesis. Li, B. Y., Birdwell, C. and Whelan, J., J. Lipid, Res., Vol. 5, 1869-1877 (1994). Eicosapentaenoic acid levels in colonic mucosal phospholipids are negatively associated with indices of cell proliferation. Lee, D.-Y. K., Lupton, J. R., Aukema, H. M. and Chapkin, R. S., J. Nutr., Vol. 123, 1808-1917 (1993). Conversely, arachidonic acid content in colonic mucosal phospholipids is associated with higher indices of cell proliferation. Lee, D.-Y. K., Lupton, J. R., Aukema, H. M. and Chapkin, R. S., J. Nutra., Vol. 123, 1808-1917 (1993).
More recently, Paulson et al. showed that a fish oil derived concentrate of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) decreased intestinal polyp formation and growth in xcex94716 Apc knockout Min/+ mice. Carcinogenesis, Vol. 18, 1905-1910 (1997). Similarly, Oshima et al. showed that dietary DHA-ethyl ester reduced intestinal polyp development in xcex94716 Apc knockout Min/+ mice. Carcinogenesis, Vol. 18, 2605-2607 (1995). Moser, A. R., Lougo, C., Gould, K. A., McNeley, M. K., Shoemaker, A. R., Dove, W. F., Eur. J. Cancer, 31A(7-8), 1061-1064 (1995).
European patent application No. 0 440 307 A2 discloses compositions for use in the treatment of breast cancer. The disclosed compositions contain one or more metabolites of xcex1-linolenic acid and one or more metabolites of linoleic acid.
International Application No. 97/39749 describes methods for the prevention and treatment of cachexia and anorexia. Cachexia and anorexia are said to be common conditions among cancer patients whose diseases have progressed to metastatic cancer. The disclosed methods involve administering to an individual an oil blend containing n-6 and n-3 fatty acids, a source of amino-nitrogen which includes branched-chain amino acids, and an antioxidant component.
U.S. Pat. No. 5,886,037 discloses food compositions for treatment of various diseases which may be associated with the metabolic syndrome (syndrome X), including hyperlipoproteinaemia, obesity, hyperuricemia, hypertension, fatty liver, diabetes type II, insulin resistance and atherosclerotic vascular disease. The disclosed compositions contain medium-chain fatty acids and n-3 polyunsaturated long chain fatty acids.
U.S. Pat. No. 5,158,975 describes the use of stearidonic acid for prevention and treatment of inflammatory conditions, including allergic disorders, skin disorders, rheumatic disorders, and those following trauma, shock and pathologies. Stearidonic acid (SDA) and its metabolites, EPA and DHA, are said to inhibit biosynthesis of leukotrienes which are involved in the inflammation process.
U.S. Pat. No. 5,562,913 describes a method of treating n-6 or n-3 essential fatty acid deficits in smokers. The method involves administering to the smoker a formulation containing an n-6 essential fatty acid, an n-3 essential fatty acid, or a mixture of n-6 and n-3 fatty acids.
The present invention is directed towards a method for treating or preventing cancer in a mammal. The method involves administering to a mammal in need thereof a cancer inhibiting amount of stearidonic acid (18:4 n-3), eicosatetraenoic acid (20:4 n-3), docosapentaenoic acid (22:5 n-3) or mixtures thereof.